Bottom Line:
Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h.Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points.Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo.

ABSTRACTWe examined the neuroprotective efficacy of docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, in acute ischemic stroke; studied the therapeutic window; and investigated whether DHA administration after an ischemic stroke is able to salvage the penumbra. In each series described below, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo). In series 1, DHA or saline was administered i.v. at 3, 4, 5, or 6 h after stroke. In series 2, MRI was conducted on days 1, 3 and 7. In series 3, DHA or saline was administered at 3 h, and lipidomic analysis was conducted on day 3. Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h. Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points. Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo. DHA administration provides neurobehavioral recovery, reduces brain infarction and edema, and activates NPD1 synthesis in the penumbra when administered up to 5 h after focal cerebral ischemia in rats.

Fig3: MRI study: a DHA improved neurological scores on days 3 and 7. b T2 hyperintensites were observed in the cortex and striatum of saline-treated rats, consistent with edema formation. In contrast, DHA reduced edema with little T2 hyperintensities at day 3 and not at all at day 7, resulting in an intact corpus callosum at day 7. c DHA reduced T2 values within the lesion computed from T2WI on days 1, 3, and 7, consistent with decreased edema. Data are means ± SEM. Asterisk, significantly different from saline-treated group (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). d 3D infarct volumes were computed from T2WI on days 1, 3, and 7 after MCAo. Saline-treated rats showed large cortical and subcortical infarct volumes that slowly decreased over the course of 7 days. By contrast, infarct volume was dramatically reduced in rats treated with DHA and was mostly localized in the subcortical areas. 3D reconstructions are from the same animal in each group over the 7-day time course

Mentions:
When DHA was given 3 h after MCAo onset, the neurological scores were significantly improved on days 3 (p < 0.01) and 7 (p < 0.02; Fig. 3a). Also, initial smaller infarcts were only localized to the striatum on day 1 and were indistinguishable from normal tissues by day 7 (Fig. 3b). T2WI revealed large cortical and striatial infarctions in saline rats that resolved over 7 days (Fig. 3b). DHA yielded reduced T2 values (decreased edema) within the lesion (p < 0.002), and there were no differences in T2 values for the contralateral tissues (Fig. 3c). There was a difference in the ADC within the infarcted lesion when comparing saline and DHA rats at days 1, 3, and 7 after MCAo. The ipsilateral ADC value was increased at days 1 and 7 (p < 0.001). However, the ADC in DHA was 21% lower at day 3. These dynamic processes reflect repair mechanisms within the DHA-rat lesion. Interestingly, ADC was increased in the DHA contralateral lesion. Three-dimensional infarct volumes were computed from T2WI (presented in Fig. 3d).Fig. 3

Fig3: MRI study: a DHA improved neurological scores on days 3 and 7. b T2 hyperintensites were observed in the cortex and striatum of saline-treated rats, consistent with edema formation. In contrast, DHA reduced edema with little T2 hyperintensities at day 3 and not at all at day 7, resulting in an intact corpus callosum at day 7. c DHA reduced T2 values within the lesion computed from T2WI on days 1, 3, and 7, consistent with decreased edema. Data are means ± SEM. Asterisk, significantly different from saline-treated group (p < 0.05; repeated-measures ANOVA followed by Bonferroni tests). d 3D infarct volumes were computed from T2WI on days 1, 3, and 7 after MCAo. Saline-treated rats showed large cortical and subcortical infarct volumes that slowly decreased over the course of 7 days. By contrast, infarct volume was dramatically reduced in rats treated with DHA and was mostly localized in the subcortical areas. 3D reconstructions are from the same animal in each group over the 7-day time course

Mentions:
When DHA was given 3 h after MCAo onset, the neurological scores were significantly improved on days 3 (p < 0.01) and 7 (p < 0.02; Fig. 3a). Also, initial smaller infarcts were only localized to the striatum on day 1 and were indistinguishable from normal tissues by day 7 (Fig. 3b). T2WI revealed large cortical and striatial infarctions in saline rats that resolved over 7 days (Fig. 3b). DHA yielded reduced T2 values (decreased edema) within the lesion (p < 0.002), and there were no differences in T2 values for the contralateral tissues (Fig. 3c). There was a difference in the ADC within the infarcted lesion when comparing saline and DHA rats at days 1, 3, and 7 after MCAo. The ipsilateral ADC value was increased at days 1 and 7 (p < 0.001). However, the ADC in DHA was 21% lower at day 3. These dynamic processes reflect repair mechanisms within the DHA-rat lesion. Interestingly, ADC was increased in the DHA contralateral lesion. Three-dimensional infarct volumes were computed from T2WI (presented in Fig. 3d).Fig. 3

Bottom Line:
Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h.Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points.Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo.

ABSTRACTWe examined the neuroprotective efficacy of docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, in acute ischemic stroke; studied the therapeutic window; and investigated whether DHA administration after an ischemic stroke is able to salvage the penumbra. In each series described below, SD rats underwent 2 h of middle cerebral artery occlusion (MCAo). In series 1, DHA or saline was administered i.v. at 3, 4, 5, or 6 h after stroke. In series 2, MRI was conducted on days 1, 3 and 7. In series 3, DHA or saline was administered at 3 h, and lipidomic analysis was conducted on day 3. Treatment with DHA significantly improved behavior and reduced total infarct volume by a mean of 40% when administered at 3 h, by 66% at 4 h, and by 59% at 5 h. Total lesion volumes computed from T2-weighted images were reduced in the DHA group at all time points. Lipidomic analysis showed that DHA treatment potentiates neuroprotectin D1 (NPD1) synthesis in the penumbra 3 days after MCAo. DHA administration provides neurobehavioral recovery, reduces brain infarction and edema, and activates NPD1 synthesis in the penumbra when administered up to 5 h after focal cerebral ischemia in rats.